myophysiology 4

1. Neuromuscular Junction

2. • Neuromuscular junction: is the junction
between terminal branch of the nerve fiber and
muscle fiber.
• STRUCTURE OF NEUROMUSCULAR JUNCTION:
1. Axon Terminal.
2. Synaptic Trough or Gutter.
3. Synaptic Cleft or space.
4. Subneural Clefts.

3. In the axon terminal are
many mitochondria that
supply adenosine
triphosphate (ATP), the
energy source that is used
for synthesis of an
excitatory transmitter,
acetylcholine.
In the synaptic
space are large quantities of
the enzyme
acetylcholinesterase,
which destroys
acetylcholine a few
milliseconds after it has
been released from the
synaptic vesicles.

4. SECRETION OF ACETYLCHOLINE
BY THE NERVE TERMINALS:
• A nerve impulse reaches the neuromuscular junction.
• About 125 vesicles of acetylcholine are released from the terminals into the
synaptic space.
1. On the inside surface of the neural membrane are linear dense bars.
2. To each side of each dense bar are protein particles that penetrate the neural
membrane; these are voltage-gated calcium channels.
3. Calcium ions to diffuse from the synaptic space to the interior of the nerve
terminal.
4. Calcium ions, in turn, are believed to activate Ca2+-calmodulin dependent
protein kinase, which, in turn, phosphorylates synapsin proteins that anchor the
acetylcholine vesicles to the cytoskeleton of the presynaptic terminal.
5. Acetylcholine vesicles move to the active zone of the presynaptic neural
membrane adjacent to the dense bars.
6. The vesicles then dock at the release sites, fuse with the neural membrane, and
empty their acetylcholine into the synaptic space by the process of exocytosis.
7. Acetylcholine Opens Ion Channels (Voltage - gated Na channel )on Postsynaptic
Membranes.

8. • Destruction of the Released Acetylcholine by Acetylcholinesterase:
(1) Most of the acetylcholine is destroyed by the enzyme
acetylcholinesterase.
(2) a small amount of acetylcholine diffuses out of the synaptic space and is
then no longer available to act on the muscle fiber membrane.
• End Plate Potential and Excitation of the Skeletal Muscle Fiber:
• The sudden insurgence of sodium ions into the muscle fiber when the
acetylcholine-gated channels open causes the electrical potential inside
the fiber at the local area of the end plate to increase in the positive
direction as much as 50 to 75 millivolts, creating a local potential called
the end plate potential.
• Safety Factor for Transmission at the Neuromuscular Junction; Fatigue
of the Junction:
• Each impulse that arrives at the neuromuscular junction causes about
three times as much end plate potential as that required to stimulate the
muscle fiber “Safety Factor ”.
• Stimulation of the nerve fiber at rates greater than 100 times per second
for several minutes often diminishes the number of acetylcholine vesicles
so much that impulses fail to pass into the muscle fiber “Fatigue”.

10. Drugs That Enhance or Block
Transmission at the Neuromuscular
Junction:
• Drugs That Stimulate the Muscle Fiber by Acetylcholine-
Like Action:
• Methacholine, carbachol, and nicotine.
• Drugs That Stimulate the Neuromuscular Junction by
Inactivating Acetylcholinesterase:
• neostigmine, physostigmine, and diisopropyl
fluorophosphate.
• Drugs That Block Transmission at the Neuromuscular
Junction:
• A group of drugs known as curariform drugs can prevent
passage of impulses from the nerve ending into the muscle.
• Action Potentials Spread to the Interior of the Muscle
Fiber by Way of “Transverse Tubules”.

11. • Excitation-contraction coupling in
skeletal muscle.
• The top panel shows an action
potential in the transverse tubule
that causes a conformational
change in the voltage-sensing
dihydropyridine (DHP) receptors,
opening the Ca++ release
channels in the terminal cisternae
of the sarcoplasmic reticulum and
permitting Ca++ to rapidly diffuse
into the sarcoplasm and initiate
muscle contraction.
• During repolarization (bottom
panel), the conformational
change in the DHP receptor closes
the Ca++ release channels and
Ca++ is transported from the
sarcoplasm into the sarcoplasmic
reticulum by an adenosine
triphosphate–dependent calcium
pump.calsequestrin is protein that can bind up to 40
times more calcium.

12. Excitation-contraction coupling in the muscle:
(1) an action potential that causes release of calcium ions from the sarcoplasmic reticulum.
(2) Re-uptake of the calcium ions by a calcium pump.
A Calcium Pump Removes Calcium Ions from the Myofibrillar Fluid After Contraction
Occurs.